Double diastereocontrol in bifunctional thiourea organocatalysis: Iterative Michael-Michael-Henry sequence regulated by the configuration of chiral catalysts

Article abstract of DOI:10.1021/ol201559j

The importance and reactivity consequences of the double diastereocontrol in noncovalent bifunctional organocatalysis were studied. The results suggest that the bifunctional thioureas can have synthetic limitations in multicomponent domino or autotandem catalysis. Nevertheless, we provided a means to exploit this behavior and used the configuration of the chiral catalyst as a control element in organo-sequential reactions.

Full text of DOI:10.1021/ol201559j

ORGANIC
LETTERS
2011
Vol. 13, No. 20
5416–5419
Double Diastereocontrol in Bifunctional
Thiourea Organocatalysis: Iterative
MichaelÀMichaelÀHenry Sequence
Regulated by the Configuration of Chiral
Catalysts
†
Szilard Varga, Gergely Jakab, Laszlo Drahos, Tamas Holczbauer,
†
‡
‡
ꢀ
ꢀ ꢀ
Matyas Czugler, and Tibor Soos*
ꢀ
ꢀ
ꢀ
‡
,†
ꢀ
Institute of Biomolecular Chemistry, Chemical Research Center of Hungarian Academy
of Sciences, P.O. Box 17, 1525 Budapest, Hungary, and Institute of Structural Chemistry,
Chemical Research Center of Hungarian Academy of Sciences, P.O. Box 17,
1525 Budapest, Hungary
tibor.soos@chemres.hu
Received June 10, 2011
ABSTRACT
The importance and reactivity consequences of the double diastereocontrol in noncovalent bifunctional organocatalysis were studied. The results
suggest that the bifunctional thioureas can have synthetic limitations in multicomponent domino or autotandem catalysis. Nevertheless, we
provided a means to exploit this behavior and used the configuration of the chiral catalyst as a control element in organo-sequential reactions.
As a frontier discipline, asymmetric organocatalysis
has contributed greatly to the past decade’s advances
in synthetic organic chemistry.1 One of its impressive
and current applications is the construction of complex
molecules via domino or cascade reactions.2,3 To date,
the majority of organo-cascade procedures rests upon
primary amine,4 secondary amine,5 or Brønsted acid6
catalysis. The bifunctional thioureas, contrary to their
commanding organocatalytic performance, have seen
much less utilization in multicomponent reactions.7 Thus,
(3) Pioneering works on organo-cascade reactions: (a) Bui, T.; Barbas,
C. F., III. Tetrahedron Lett. 2000, 41, 6951. (b) Halland, N.; Aburel, P. S.;
Jørgensen, K. A. Angew. Chem., Int. Ed. 2004, 43, 1272. (c) Rueping, M.;
Antonchick, A. P.; Theissmann, T. Angew. Chem., Int. Ed. 2006, 45, 3683.
(d) Huang, Y.; Walji, A. M.; Larsen, C. H.; MacMillan, D. W. C. J. Am.
† Institute of Biomolecular Chemistry.
‡ Institute of Structural Chemistry.
(1) (a) Asymmetric Organocatalysis; Berkessel, A., Groger, H., Eds.;
Wiley-VCH: Weinheim, Germany, 2005. (b) Enantioselective Organo-
catalysis; Dalko, P. I., Ed.; Wiley-VCH: Weinheim, Germany, 2007.
(c) Hydrogen Bonding in Organic Synthesis; Pihko, P., Ed.; Wiley-VCH:
Weinheim, Germany, 2009. (d) A special issue on asymmetric organocata-
lysis: Chem. Rev. 2007, 107, 5413. (e) Melchiorre, P.; Margio, M.;
Armando, A.; Bartoli, G. Angew. Chem., Int. Ed. 2008, 47, 6138.
(f) Marcelli, T.; Hiemstra, H. Synthesis 2010, 1229.
€
ꢀ
Chem. Soc. 2005, 127, 15051. (e) Marigo, M.; Schulte, T.; Franzen, J.;
€
Jørgensen, K. A. J. Am. Chem. Soc. 2005, 127, 15710. (f) Enders, D.; Huttl,
M. R. M.; Grondal, C.; Raabe, G. Nature 2006, 441, 861.
(4) Selected organo-cascade reactions with primary amine catalysts:
(a) Wu, L.-Y.; Bencivenni, G.; Mancinelli, M.; Mazzanti, A.; Bartoli, G.;
Melchiorre, P. Angew. Chem., Int. Ed. 2009, 48, 7196. (b) Bencivenni, G.;
Wu, L.-Y.; Mazzanti, A.; Giannichi, B.; Pesciaioli, F.; Song, M.-P.;
Bartoli, G.; Melchiorre, P. Angew. Chem., Int. Ed. 2009, 48, 7200.
(c) Galzerano, P.; Pesciaioli, F.; Mazzanti, A.; Bartoli, G.; Melchiorre, P.
Angew. Chem., Int. Ed. 2009, 48, 7892.
(2) (a) Excellent review on tandem catalysis with taxonomy: Fogg,
D. E.; dos Santos, E. N. Coord. Chem. Rev. 2004, 248, 2365. (b) Recent
€
review: Enders, D.; Grondal, C.; Huttl, M. R. M. Angew. Chem., Int. Ed.
2007, 46, 1570.
r
10.1021/ol201559j
Published on Web 09/14/2011
2011 American Chemical Society

it would be of interest to know whether a mechanistic
reason exists behind this apparent disparity. In this paper,
we report our synthetic studies which aimed to explore the
capabilities of bifunctional thioureas in a Michael-type
organo-cascade reaction. As a result, an interesting regu-
latory mechanism for the catalytic cycle was noticed: the
chiral product of the first Michael step inhibited its own
further reaction. Nevertheless, this seemingly restrictive
effect, which turned out to be the exaggerated form of the
double diastereocontrol, was alleviated and beneficially
exploited for the iterative assembly of densely functiona-
lized cyclohexanes.
addition reactions.9 Despite the catalytic advantage
offered by the dual activation, the application of these
bifunctional catalysts (or their analogs) was scarce in multi-
component reactions. Therefore, a synthetic study was
initiated to uncover any structural or mechanistic reasons
which could adversely affect a cascade reaction. We envi-
saged a thiourea 1a catalyzed MichaelÀ(MichaelÀHenry)
stepwise sequence (Figure 1) as a model of a cascade process.
First, the enantioenriched R-6a was formed in an organo-
catalytic Michael addition of nitromethane (4) to chalcone
5a.8a,b In the second and separate step, we probed construct-
ing a cyclohexane derivative 8 in a catalytic MichaelÀHenry
sequence using the same catalyst and conditions. Despite the
high reactivity of nitrostyrene 7a, however, we were unable
to detect 8 or any addition products after 1 week.
The bifunctional quinine organocatalyst 1a,b and its
pseudoenantiomer 28 have became a versatile tool in
organocatalysis, especially in asymmetric 1,2- and 1,4-
(5) Reviews on organo-cascade reactions with secondary amine
catalysts: (a) Bertelsen, S.; Jørgensen, K. A. Chem. Soc. Rev. 2009, 38,
2178. (b) Grondal, C.; Jeanty, M.; Enders, D. Nat. Chem. 2010, 2, 167.
(c) Westermann, B.; Ayaz, M.; van Berkel, S. S. Angew. Chem., Int. Ed.
2010, 49, 846. Selected examples:(d) Lu, M.; Zhu, D.; Lu, Y.; Hou, Y.;
Tan, B.; Zhong, G. Angew. Chem., Int. Ed. 2008, 47, 10187. (e) Chandler,
C.; Galzerano, P.; Michrowska, A.; List, B. Angew. Chem., Int. Ed.
2009, 48, 1978. (f) Rueping, M.; Kuenkel, A.; Tato, F.; Bats, J. W.
Angew. Chem., Int. Ed. 2009, 48, 3699. (g) Simmons, B.; Walji, A. M.;
MacMillan, D. W. C. Angew. Chem., Int. Ed. 2009, 48, 4349. (h) Jiang,
H.; Elsner, P.; Jensen, K. L.; Falcicchio, A.; Marcos, V.; Jørgensen,
K. A. Angew. Chem., Int. Ed. 2009, 48, 6844. (i) Hong, B.-C.; Kotame, P.;
Tsai, C.-W.; Liao, J.-H. Org. Lett. 2010, 12, 776. (j) Enders, D.; Wang,
C.; Mukanova, M.; Greb, A. Chem. Commun. 2010, 46, 2447. (k) Ma, A.;
Ma, D. Org. Lett. 2010, 12, 3634.
(6) Selected examples of Brønsted acid catalyzed reactions: (a) Zhou,
J.; List, B. J. Am. Chem. Soc. 2007, 129, 7498. (b) Terada, M.; Machioka,
K.; Sorimachi, K. J. Am. Chem. Soc. 2007, 129, 10336. (c) Muratore,
M. E.; Holloway, C. A.; Pilling, A. W.; Storer, R. I.; Trevitt, G.; Dixon,
D. J. J. Am. Chem. Soc. 2009, 131, 10796. (d) Akiyama, T.; Katoh, T.;
Mori, K. Angew. Chem., Int. Ed. 2009, 48, 4226. (e) Albert, B. J.;
Yamamoto, H. Angew. Chem., Int. Ed. 2010, 49, 2747.
(7) A successful MichaelÀMichael two-component cascade reaction
was reported using Takemoto’s bifunctional thiourea catalyst. The one-
pot domino method has limited applicability, and it was generally less
efficient than the two-step cyclization using TMG or KOH bases in the
second step: (a) Hoashi, Y.; Yabuta, T.; Yuan, P.; Miyabe, H.;
Takemoto, Y. Tetrahedron 2006, 62, 365. A rather similar case using
bifunctional cinchonas: (b) He, P.; Liu, X.; Shi, J.; Lin, L.; Feng, X.
Org. Lett. 2011, 13, 939. A MichaelÀMichael two-component cascade
reaction with DKR interplay using thiourea catalyst 1: (c) Wang, J.; Xie,
H.; Li, H.; Zu, L.; Wang, W. Angew. Chem., Int. Ed. 2008, 47, 4177.
(d) Yu, C.; Zhang, Y.; Song, A.; Ji, Y.; Wang, W. Chem.;Eur. J. 2011,
17, 770. (e) Wang, X.-F.; Hua, Q.-L.; Cheng, Y.; An, X.-L.; Yang, Q.-Q.;
Figure 1. Bifunctional thiourea catalysts and stepwise multi-
component organocatalytic strategy to construct cyclohexane
derivative 8.
The unsuccessful initial experiment prompted us to
investigate its mechanistic origin. In addition to the failure
of the second step, we also attempted to find a rationale for
the exclusivemonoadductformation inthe first step. These
two cases are analogous and seem to be mechanistically
related. As a working hypothesis, we supposed that the
incapacity of catalyst 1a for the second Michael addition
arose from an intriguing situation of double diastereo-
control.10,11 Specifically, the combination of the chiral cat-
alyst 1aandits chiralproductR-6agenerates amismatched
pair with a sufficiently high barrier to the succeeding
Chen, J.-R.; Xiao, W.-J. Angew. Chem., Int. Ed. 2010, 49, 8379.
A
multicomponent organo-cascade reaction, thiourea catalyst 1 and 2 (or
their analogs) were applied in orthogonal tandem catalytic procedures
(combined with JørgensenÀHayashicatalyst). (f) Wang, Y.; Han, R.-G.;
Zhao, Y.-L.; Yang, S.; Xu, P.-Y.; Dixon, D. J. Angew. Chem., Int. Ed.
2009, 48, 9834. (g) Wang, Y.; Yu, D.-F.; Liu, Y.-Z.; Wei, H.; Luo, Y.-C.;
Dixon, D. J.; Xu, P.-Y. Chem.;Eur. J. 2010, 16, 3922. (h) Ren, Q.; Gao,
Y.; Wang, J. Chem.;Eur. J. 2010, 16, 13594. (i) Gao, Y.; Ren, Q.; Wu,
H.; Li, M.; Wang, J. Chem. Commun. 2010, 46, 9232. (j) Gao, Y.; Ren,
Q.; Siau, W.-Y.; Wang, J. Chem. Commun. 2011, 47, 5819. (k) Corrri-
gendum: An exceptional MichaelÀMichaelÀHenry cascade promoted
by a bifunctional thiourea catalyst. Basle, O.; Raimondi, W.; del Mar
Sanchez Duque, M.; Bonne, D.; Constantieux, T.; Rodriguez, J. Org.
Lett. 2010, 12, 5246À5249.
(10) For details about double diastereocontrol, see: (a) Walsh, P. J.;
Kozlowski, M. C. Fundamentals of Asymmetric Catalysis; University
Science Books: Sausalito, CA, 2009. (b) Masamune, S.; Choy, W.; Petersen,
J. S.; Sita, L. R. Angew. Chem., Int. Ed. 1985, 24, 1. (c) Sharpless, K. B.
Chem. Scr. 1985, 25, 71. (d) Evans, D. A.; Kozlowski, M. C.; Murry,
J. A.; Burgey, C. S.; Campos, K. R.; Conell, B. T.; Staples, R. J. J. Am.
Chem. Soc. 1999, 121, 669.
(11) Recent organocatalytic examples of double diastereocontrol
(predominant external, catalyst control): (a) Alcaide, B.; Almendros,
P.; Luna, A.; Torres, M. R. J. Org. Chem. 2006, 71, 4818. (b) Gryko, D.;
(8) Our work on bifunctional organocatalysis: (a) Vakulya, B.;
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(c) Vakulya, B.; Varga, Sz.; Soos, T. J. Org. Chem. 2008, 73, 3475.
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(d) Tarkanyi, G.; Kiraly, P.; Varga, Sz.; Vakulya, B.; Soos, T. Chem.;
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Eur. J. 2008, 14, 6078. (e) Kiraly, P.; Soos, T.; Varga, Sz.; Vakulya, B.;
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Tarkanyi, G. Magn. Reson. Chem. 2010, 48, 13.
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Zimnicka, M.; Lipinski, R. J. Org. Chem. 2007, 72, 964. (c) Crisostomo,
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Comm 2008, 2499. Seminal references: (b) Li, B.-J.; Jiang, L.; Liu, M.;
Chen, Y.-C. Synlett 2005, 603. (c) Reference 8a. (d) McCooey, S. H.;
Connon, S. J. Angew. Chem., Int. Ed. 2005, 44, 6367. (e) Ye, J.; Dixon,
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Org. Lett., Vol. 13, No. 20, 2011
5417

intermolecular reaction; thus, the subsequent organocata-
lytic step becomes kinetically unfavorable.
the formation of an insoluble nitrostryrene polymer in the
above reactions, we used a 1 molar excess of nitrostyrene
7a to further increase the yield of l-9a. Using the most
efficient catalyst 1a, one can reduce the catalyst load to
1 mol % withouta deleterious effectonselectivity (entry 8).
Additionally, no significant effect of dilution on the yield
and selectivity was detected (entry 10).
Totestthevalidityofdoublediastereocontrol asasource
of inhibition, a reaction sequence was devised having a
presumably matched case for the second step (Scheme 1).
Accordingly, not the thiourea catalyst 1a but its pseudoe-
nantiomer 2 was probed for the follow-up MichaelÀHenry
reaction. To our delight, the enantiomerically enriched
Michael adduct R-6a underwent a smooth catalytic reac-
tion with nitroolefin 7a. The catalyst 2 also had an in-
fluence on the stereochemical outcome of the reaction: the
enantiopurity increased further (>99% ee) and near full
control of diastereoselectivity was achieved (>99:1 dr).
Additionally, executing this iterative startegy in a one-pot
manner (adding the second catalyst and the reagent after
the first Michael addition finished) has no additive advan-
tage; the pseudoenantiomeric catalysts mutually blocked
their activities, affording the expected product 9a in a
markedly lower yield (<5%).
Table 1. Optimization of Reaction Conditions
entrya
cat.
cat. load solvent 7a equiv yieldb
eec
1
1b
1b
1b
1b
1a
1c
1a
1a
1a
1a
TEA
3
10%
10%
10%
10%
10%
10%
10%
1%
CH2Cl2
CH3CN
Et2O
1
1
1
1
1
1
2
2
2
2
2
2
46%
16%
42%
54%
62%
36%
73%
48%
77%
76%
À
98%
2
96%
3
98%
4
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
>99%
>99%
>99%
>99%
>99%
>99%
>99%
À
Scheme 1. Iterative Noncovalent Organocatalytic Strategy to
Assemble Cyclohexane Derivatives 9a
5
6
7
8
9
5%
10d
11e
12
10%
10%
10%
19%
93%f
a Unless otherwise noted, all reactions were performed with S-6a
(0.5 mmol), β-nitrostyrene (7a), and added catalyst in 1.2 mL of solvent
at room temperature for 2 days. b Yield of the isolated product.
c Determined by chiral HPLC analysis; the diastereomeric ratio was
>99:1. d 2.4 mL of toluene were applied in this reaction. e Triethyl amine
as catalyst was employed. f The diastereomeric ratio was slightly less
than previous cases: 91:7:2.
Interestingly, four out of the five chiral centers of cyclo-
hexane d-9a were established in the second reaction step and
not every substituent occupied the thermodynamically pre-
ferred equatorial positions. The employment of the catalysts
1a and 2 in the reverse order led to the expected inversion of
the stereochemistry in l-9a. The absolute stereochemical
relationships were confirmed by X-ray single crystal struc-
ture determinations of two inclusions of l-9a.
After demonstrating the capacity of thiourea catalysts 1
and 2 in sequential reactions to construct complex mole-
cular architectures, we proceeded to investigate the influ-
ence of further experimental parameters, such as solvent,
catalyst type and load, and reagents’ stoichiometry. As
expected for bifunctional noncovalent organocatalysis, the
reaction was more rapid and efficient in a less polar
medium (Table 1, entry 4 vs 2). Additionally, the solvent
polarity had no profound effect on the stereochemical effi-
ciency. An interesting feature of the bifunctional thiourea
cinchona catalysts is that the catalyst activity can be fine-
tuned by modification of the remote vinyl group of the qui-
nuclidine moiety. Probing catalyst systems 1aÀc showed
no significant difference between their activities, although
the most basic 1a promoted the formation of l-9a with the
highest conversion (entries 4À6). Since we always detected
It also became apparent that a bifunctional catalyst is
required to ensure the formation of the functionalized
cyclohexane product l-9a, since base catalysis alone was
insufficient (entry 11).12 The achiral bifunctional analog 3,
however, was able to promote the MichaelÀHenry seq-
uence. Although its catalytic efficiency is markedly less
than that of 1a (entry 7 vs 12), the astonishing feature of
the reaction is the enormous level of asymmetric induction
by only one stereocenter; high diastereoselectivity was
achieved in the formation of four new stereocenters.
Apparently, the bifunctional achiral catalyst 3 was able
to restrict the conformational freedom of both substrates
and created a highly rigid transition state. It seems plau-
sible that a combination of the sterical shielding and
the coordinating ability of the substituents of the control-
ling stereocenter was necessary for the observed high
diastereoselectivity.13 This dual action could also explain
(12) Recent example of substrate controlled organocatalytic Henry
reaction affording high diastereoselectivity by an achiral base: Uehara,
ꢀ
H.; Imashiro, R.; Hernandez-Torres, G.; Barbas, C. F., III. Proc. Natl.
Acad. Sci. U.S.A. 2010, 107, 20672.
(13) For factors governing the stereoselectivity, see: Hoffmann,
R. W. Chem. Rev. 1989, 89, 1841.
5418
Org. Lett., Vol. 13, No. 20, 2011

the occurrence of the unusual form of double diastereo-
control. Finally, the above experiments indicate that the
chiral substrate exerted a predominant influence on the
subsequent asymmetric reaction; thus internal diastereo-
control was occurring.
Then we continued to explore the applicability of a
variety of enantiomerically enriched Michael adducts R-
6iÀqintheMichaelÀHenrysequence.AsshowninTable2,
different electron-withdrawing and -donating substituents
were well tolerated in the meta or para position of the
aromatic rings (entries 8À13). However, no further reac-
tion occurred when Michael adducts R-6o,p had an ali-
phatic substituent at the R1 position (entries 14, 15).
Nevertheless, the structurally similar olefinic derivative
6q could be transformed to the cyclohexane product 9q
in the organocatalytic process (entry 16). These observa-
tions indicate that an additional πÀπ interaction might be
involved in these organocatalytic reactions. Due to the
unique case of double stereocontrol, we reasoned that the
bifunctional thioureas could also be used for the kinetic
resolution of racemic Michael adducts rac-6a,r. As ex-
pected, the matched reactions were more rapid and highly
selective kinetic resolutions were achieved. Thus, the cy-
clohexane products 9a,r formed with high enantio- and
diastereoselectivity (entries 17, 18). Since the conversions
were less than 50%, the synthetic utility of these kinetic
resolutions is mediocre. Nevertheless, it is an intriguing
procedure allowing access to highly enantioenriched com-
pounds via two CÀC bond forming reactions.
Table 2. Investigation of the Scope of the Double Stereodiffer-
entiating MichaelÀHenry Type Reaction
entrya
R1, R2, R3
product yieldb
eec
drd
1
2
3
Ph, Ph, 2-Cl-C6H4
Ph, Ph, c-Hex
d-9b
d-9c
d-9d
À
À
À
À
À
À
Ph, Ph,
40% >99% 93:7
3,4-(MeO)2-C6H3
Ph, Ph, 2-thienyl
Ph, Ph, 4-Cl-C6H4
Ph, Ph, 4-NO2-C6H4
Ph, Ph, 4-MeO-C6H4
4-Cl-C6H4, Ph, Ph
4-F-C6H4, Ph, Ph
3-Me-C6H4, Ph, Ph
Ph, 4-MeO-C6H4, Ph
Ph, 4-NO2-C6H4, Ph
Ph, 4-Cl-C6H4, Ph
c-Hex, Ph, Ph
4
d-9e
d-9f
47% 99%
>99:1
5
53% >99% 98:2
29% >99% >99:1
6
d-9g
d-9h
d-9i
7
60% 98%
94:6
8
45% >99% 99:1
46% >99% 94:6
40% >99% 95:5
In conclusion, our study showed the importance and
reactivity consequences of double diastereocontrol in non-
covalent bifunctional organocatalysis. Our results also
suggest that the bifunctional thioureas can have synthetic
limitations in multicomponent domino or autotandem
catalysis. Nevertheless, we provided a means to exploit
this behavior and used the configuration of the chiral
catalyst as a control element in organo-sequential reac-
tions. Despite not being single-operational, the merit of
this iterative method is highlighted by its efficiency to
construct stereochemically dense architectures with an
exquisite level of both enantio- and diastereoselectivities.
As an understanding of double diastereodifferentiation in
bifunctional organocatalysis emerged in our laboratory,
several additional applications were identified and will be
reported shortly.
9
d-9j
10
11
12
13
14
15
16
17e
18e
d-9k
d-9l
34% 99%
93:7
d-9m
d-9n
d-9o
d-9p
d-9q
d-9a
d-9r
68% >99% 94:6
61% 99%
95:5
À
À
À
À
À
C6H4CH2CH2, Ph, Ph
Z-C6H4CHCH, Ph, Ph
Ph, Ph, Ph
À
25% >99% 89:11
22% 88%
35% 90%
>99:1
89:11
Ph, Me, Ph
a Unless otherwise noted, the reactions were performed with
0.5 mmol of Michael adducts R-6a,iÀq, 1 mmol of nitroolefin (7aÀh),
and 0.05 mmol of catalyst 2 in 1.2 mL of toluene at room temperature for
64 h. b Combined yields of diastereoisomers. c Determined by chiral HPLC
analysis. d Determined by NMR spectroscopy. e Reaction condition:
0.5 mmol of rac-6a,r, 0.5 mmol of β-nitrostyrene (7a), and 0.05 mmol of
catalyst 2 in 1.2 mL of toluene at room temperature for 64 h.
With optimal reaction conditions established, the scope of
the above iterative procedure was investigated. First, struc-
turally different nitroolefins 7bÀh were probed as a second
electrophile (Table 2). Regardless of having electron-with-
drawing or -donating groups in the aryl ring’s meta or para
positions, nitrostyrenes 7dÀh showed similar reactivity and
selectivity in the d-9dÀh forming reaction (entries 3À7).
Among nitrostyrenes, the sterically hindered o-chloro deri-
vative 7b failed to give any adduct (entry 1). In a similar
manner, probing the aliphatic nitroolefin 7c, somewhat
surprisingly, showed no adduct formation (entry 2).
Acknowledgment. We are grateful for the financial
support from OTKA (Grants K-69086, NK-77784).
Supporting Information Available. Experimental pro-
cedures, spectral data, X-ray crystal structure, and CIFs.
This material is available free of charge via the Internet at
http://pubs.acs.org.
Note Added after ASAP Publication. Reference 7k was
added, and the paper was reposted September 16, 2011.
Org. Lett., Vol. 13, No. 20, 2011
5419